Leukocytapheresis as an adjunct to conventional medication for inflammatory bowel disease.

Abstract

Inflammatory bowel disease is characterized by clinical remission and relapse caused by severe intestinal inflammation. Drug therapy for inflammatory bowel disease is associated with unpleasant side effects. Furthermore, efficacy of conventional drugs decreases with chronic use, which can be a major difficulty in the long-term management of this disease. In active inflammatory bowel disease, leukocytes are elevated with activation behavior and increased survival time, and mucosal neutrophil level parallels the severity of intestinal inflammation and predicts relapse. Leukocyte-derived inflammatory cytokines are suspected to be major factors in the initiation and perpetuation of inflammatory bowel disease. Accordingly, leukocytes should be appropriate targets for therapy. To reduce peripheral blood level of leukocytes, centrifugation has been used to deplete peripheral blood leukocytes; this provided the initial evidence that reducing the level of peripheral blood leukocytes can benefit patients with inflammatory disease. To overcome the limitations of centrifugation, membrane filters, such as the Cellsorba trade mark column and leukocyte-adsorbing beads containing column like Adacolumn, have been developed that are direct blood perfusion systems for removing any desired level of leukocytes. In initial independent clinical studies, these two new models have produced striking clinical efficacy, safety, and a marked reduction in the dose of corticosteroids used to induce remission of active inflammatory bowel disease. Leukocytapheresis has been associated with a significant decrease in the amount of several proinflammatory cytokines produced by peripheral blood leukocytes. Accordingly, the Japan Ministry of Health has now approved both methods for the treatment of active ulcerative colitis. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy for inflammatory bowel disease to promote remission, taper conventional drug dosage, and potentially reduce the number of patients who require colectomy. The results should further understanding of the pathophysiology of inflammatory bowel disease.